Hypertension is a leading cause of death and disability affecting 50 million people in the United States and responsible for 200,000 deaths annually. Because hypertension and associated cardiovascular diseases are particularly prevalent in Louisiana, Tulane Health Sciences Center established a Hypertension and Renal Center of Excellence, which consists of investigators in the School of Medicine and the School of Public Health and Tropical Medicine. The close linkage between hypertension and renal research is due to the growing recognition that many forms of hypertension result from abnormalities in kidney function due either to primary renal disease or to abnormal hormonal or environmental influences on the kidney that affect renal hemodynamics or tubular transport function. Disorders of sodium reabsorption by the renal tubules may lead to inadequate urinary excretion of salt, and derangements in vascular control mechanisms contribute to various forms of hypertension. Inappropriate activation of the renin-angiotensin system also leads to sodium retention and the development of hypertension with ensuing progressive renal and vascular injury. The objectives of this proposal are to provide an enriched mentoring environment to our junior faculty investigators so that they can achieve independent status and national competitiveness and to augment and strengthen biomedical research capacity at Tulane and the state of Louisiana in hypertension and associated renal and cardiovascular disease. The individual projects ranging from basic studies on development and function of the kidney to clinical and epidemiologic studies have been designed and will be performed by the junior faculty investigators who will be mentored by senior experienced faculty. Projects designated for initial support include investigations on the roles of angiotensin receptors in the control of the renal microvasculature and in kidney development and the roles of the newly described Heme-Heme oxygenase-carbon monoxide system and of cytochrome P450 metabolites in experimental and clinical hypertension. Epidemiologic studies will evaluate the effects of lifestyle modification (exercise) on hypertension in order to reduce blood pressure-related cardiovascular and renal disease in general but with emphasis on African-Americans. Accordingly, this COBRE will provide pivotal support needed to increase the number of competitive scientists in Louisiana in a disease specific area of extremely high biomedical relevance.